| Texto completo | |
| Autor(es): |
Mitre, Lucas Pari
;
Ivanov, Giovana Zanetti
;
Shams, Shahin
;
Yamaguchi, Fabio
;
Petraconi, Andre
;
Andrade, Ricardo Jorge Espanhol
;
Silva, Eduardo
;
Martin, Leonardo
;
Stilhano, Roberta Sessa
Número total de Autores: 9
|
| Tipo de documento: | Artigo Científico |
| Fonte: | FRONTIERS IN PHARMACOLOGY; v. 16, p. 16-pg., 2025-12-12. |
| Resumo | |
Introduction Volumetric muscle loss (VML) remains a major clinical challenge due to the limited capacity of skeletal muscle to regenerate large-scale injuries. Muscle-derived stem cells (MDSCs) represent a promising therapeutic option for tissue regeneration; however, their clinical application is constrained by poor post-transplantation viability and limited engraftment. Alginate hydrogels offer a supportive three-dimensional microenvironment capable of encapsulating cells, promoting their survival, and enhancing paracrine signaling through the sustained release of growth factors.Methods In this study, we developed and characterized MDSC spheroids and evaluated their regenerative potential when encapsulated in RGD-modified alginate hydrogels. Co-culture with endothelial cells significantly enhanced spheroid viability, indicating beneficial paracrine interactions. To further refine this strategy, 5% of the MDSCs were preconditioned with vascular endothelial growth factor (VEGF) prior to spheroid formation and encapsulation, integrating a pharmacological preconditioning step into the cell-hydrogel platform. Encapsulated spheroids were implanted into a murine model of VML.Results After 30 days, animals treated with alginate-encapsulated MDSC spheroids containing a 5% VEGF-preconditioned subfraction exhibited reduced granulation tissue, fewer degenerating myofibers, lower fibrosis, and improved early rota-rod performance compared with untreated and scaffold-only controls.Discussion Together, these findings highlight a pioneering proof-of-concept platform that combines 3D MDSC spheroids, alginate-based delivery, and VEGF-mediated pharmacological preconditioning for VML repair. As a 100% unconditioned MDSC+alginate group was not included, the present study should not be interpreted as demonstrating in vivo superiority of VEGF preconditioning over unconditioned MDSCs; instead, it provides a rationale for future head-to-head studies explicitly powered to address this question. (AU) | |
| Processo FAPESP: | 21/02645-5 - Terapia celular com células tronco derivadas do musculo esquelético murino encapsuladas por microgéis de alginato para tratamento de lesão muscular |
| Beneficiário: | Giovana Zanetti Ivanov |
| Modalidade de apoio: | Bolsas no Brasil - Mestrado |
| Processo FAPESP: | 22/12769-6 - Delivery de retalho terapêutico com esferoides de células MDSC encapsuladas pelo hidrogel de alginato como terapia regenerativa à lesão muscular in vivo |
| Beneficiário: | Lucas Pari Mitre |
| Modalidade de apoio: | Bolsas no Brasil - Iniciação Científica |
| Processo FAPESP: | 19/10922-9 - Terapia gênica e celular via microgéis de alginato para lesões musculares |
| Beneficiário: | Roberta Sessa Stilhano Yamaguchi |
| Modalidade de apoio: | Auxílio à Pesquisa - Jovens Pesquisadores |
| Processo FAPESP: | 21/00168-5 - EMU concedido no processo 2019/10922-9: QuantStudio Real Time PCR |
| Beneficiário: | Roberta Sessa Stilhano Yamaguchi |
| Modalidade de apoio: | Auxílio à Pesquisa - Programa Equipamentos Multiusuários |